A magnetic dipole stabilized solution which can be an electro-activated water is sterile and non-pyrogenic and is produced by exposing the water to a strong electrical (magnetic) field force in a tightly isolated and fully enclosed reactor space. It is capable of producing both a negative (cathodic) and a positive (anodic) stream of activated water.
Electrolysis of water, including saline solutions, is known for antimicrobial properties and for use on hard surfaces (U.S. Pat. Nos. 4,236,992 and 4,316,787). Electrolyzed water has been administered for therapeutic use through ingestion or topical administration. Published U.S. Patent Appl. No. 2006008908 discloses a beverage containing electrolyzed water and a cesium or rubidium salt for promoting longetivity. The application notes that there may be an electro-physiological imbalance that is the origin of disease and that electrolyzed water can restore optimal pH. The electrolyzed water is disclosed as an alkaline water. Published U.S. Patent Appl. No. 20050074421 discloses an acidic electrolyzed water composition. It is for external use and is purported to be a cosmetic and a hair growing tonic. An electrolyzed water composition is disclosed in U.S. Pat. No. 6,544,502. An antibiotic can be admixed in the water and used topically to treat acne. An electrolyzed saline solution containing regulated amounts of ozone and active chlorine species is described in U.S. Pat. No. 5,622,848. The solution can be given intravenously.
Cardiovascular diseases, which include coronary heart disease (heart attacks), cerebrovascular disease, raised blood pressure (hypertension), peripheral artery disease, rheumatic heart disease, congenital heart disease and heart failure, derive from dysfunctional conditions of the heart, arteries, and veins that supply oxygen to vital life-sustaining organs, including the brain and the heart itself. Major causes of cardiovascular disease are tobacco use, physical inactivity and an unhealthy diet.
Heart attacks and strokes are mainly caused by a blockage in the inner walls of the blood vessels that prevents blood from flowing to the heart or the brain. Arteriosclerosis and atherosclerosis are excess buildup of fat or plaque deposits, respectively, that cause narrowing of the veins that supply oxygenated blood to the heart and may lead to ischemic heart disease, an obstruction of blood flow to the heart. Excess fat or plaque buildup may also cause high blood pressure (hypertension), a disease known as “The Silent Killer” because the first warning sign is an angina attack, a deadly heart attack or a stroke. Kidney disorders, obesity, diabetes, smoking, excess alcohol, stress, and thyroid and adrenal gland problems can also exacerbate a high blood pressure condition.
Damage to the heart tissues from cardiovascular diseases or heart surgery disrupts the natural electrical impulses of the heart and results in cardiac arrhythmia. Sudden fluctuations in heart rate can cause cardiac irregularities and insufficiencies, including palpitations, supraventricular tachycardia, fibrillation faintness or dizziness, and even initiate a heart attack. Mismatch of cardiac output during strenuous exercise may lead to muscle damage, induce fatigue and affect athletic performance. Arteries spasm and irregular contraction and expansion of blood vessels in the brain may reduce flow of blood from the occipital lobe and trigger migraines. Levels of total blood cholesterol above 250 mg/dL, LDL cholesterol above 130 mg/dL (3.0 mmol/L), HDL cholesterol below 35 mg/dL and lipoprotein(a) level greater than 30 mg/dL may also lead to a heart attack or stroke.
Infections of the heart, known as carditis and endocarditis, may occur as a result of a weak immune system, liver problems, heart surgery, or from an autoimmune disorder like rheumatic fever.
Heavy smoking may cause Buerger's disease, also known as thrombophlebitis obliterans, an acute inflammation and thrombosis (clotting) of arteries and veins of the hands and feet, which is often associated with intense pain in the extremities, claudication in the feet and/or hands, numbness and/or tingling in the limbs, skin ulcerations, gangrene and Raynaud's phenomenon, a condition in which the distal extremities turn white upon exposure to cold.
Peripheral arterial occlusive disease may cause diabetic ulcers, which are the most common foot injuries leading to lower extremity amputation in diabetic patients.
Research indicates the course of events which leads to the loss of function, deterioration, destruction and death of the human cell and to a large extent research relates to the issue of human cellular reliance on oxygen metabolism, which occurs intracellularly. Oxygen uptake intracellularly is governed by the metabolic need for energy and takes place within the mitochondria to produce ATP, the cell's energy source. Such chemical reactions are not 100% efficient and the resultant release of highly reactive oxygen species cytoplasm are responsible for cellular damage. The relative amount of such oxygen by-products is less than the amount produced in many other mammal species, however, such by-products are highly toxic. Such examples include superoxide and hydroxyl radicals, which can cause oxidative damage to cells and tissues. Superoxide and water produce concentrated hydrogen peroxide and is capable of intense skin damage within a few seconds, when applied to human skin. The same reaction occurs intracellularly within the cytoplasm and causes severe damage. The cell are protected by means of enzymes to destroy peroxide radicals continually, however, such defenses are not 100% efficient with the result that chemical destruction of cells occurs.
Free oxygen radicals, also known as reactive oxygen species (ROS), cause much damage to macromolecules, including lipids, proteins and nucleic acids. One major toxic effect of oxygen radicals is damage to cellular membranes, including the plasma, mitochondrial and endo-membrane systems, which is initiated by lipid peroxidation and is accompanied by increased membrane rigidity, decreased activity of membrane-bound enzymes, altered activity of membrane receptors and altered membrane permeability. Furthermore, oxygen radicals can also directly attack membrane proteins and induce lipid-lipid, lipid-protein and protein-protein crosslinking, which in turn affects membrane function.
Because of their reactivity, free oxygen radicals may react with DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to cancer and malignancies. Moreover, oxygen free radicals are involved in cardiovascular diseases, the aging process, neurodegenerative diseases, including ALS, Parkinson's disease and Alzheimer's disease, cataractogenesis, atherosclerosis, diabetes mellitus, ischemia-reperfusion injury, kwashiorkor, senile- and drug-induced deafness, schizophrenia, atherosclerosis and alcohol-induced liver damage.
There is strong evidence in the literature that free oxygen radicals oxidize low density lipoprotein (LDL), which is then engulfed by phagocytes to form foam cells and plaques in the cardiovascular wall. These plaques harden and narrow the blood vessels and impair blood flow, thus depriving the heart of oxygen and nutrients. In addition, ischemia is often followed by reperfusion injury, which is caused by inadequate supplies of intracellular antioxidants. Ischemia and reperfusion are a major cause of strokes. There is also increasing evidence that mismatch of cardiac output during strenuous exercise causes release of free oxygen radicals, which contribute to muscle damage and induce fatigue and/or injury. Moreover, it has been reported that the activity of the anti-oxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) is significantly lower in subjects suffering from migraine. SOD is known to protect against vasoconstriction or vasospasm induced by superoxide radicals. Migraine is a potential risk factor or marker for atherosclerosis-related diseases.
An example of cell damage caused by oxygen reactions is damage to the DNA. It is evident that DNA destructive reactions occur daily in normal man. Most of these are repaired enzymatically, if not, such cells reproduce out of control, with resulting neoplasms. However, the long-term aging effects of endogenous damage, is exemplified by wrinkling and hardening of the skin and arteries with age. Skin and arteries consist of collagen and elastin tissue. Collagen is the major protein of white fibers of the body's connective tissues, cartilage and bone. Elastin is the major connective tissue of structures such as large blood vessels and skin. It is elastin that enables these structures to stretch and resume to original size and shape. Free radical changes described above yields a pathology, which leads to neoplastic changes, artherosclerosis and loss of elasticity of the skin. The pathology is centered on the cell membranes in all organs and affected by the supply of nutrients, vitamins, and nucleic acids through the microcirculation. Recent scientific studies have shown that this mechanism progresses from free radical reactions to oxidative products, which damages cells and tissues. This simultaneously affects all cells, tissues and organs throughout the body and is progressively insidious. These processes involve a fundamental aspect of homeostasis and cell physiology.
The clinical significance of the chemical damage generated in living cells, has been documented. It is therefore necessary to develop methods to inhibit damage caused by these mechanisms.
Circulation disorders are common disorders amongst the populace. It may be a severe medical challenge and may lead to limb loss and a marked reduction in quality of life. Circulation disorders are often diagnosed at a late stage of the disease. Non-healing small wounds are the early characteristics of poor circulation. Such wounds are often treated without the underlying cause being correctly diagnosed. This results in ulceration, discomfort and pain and may lead to limb amputation. Poor circulation can also manifest itself in a patient being able to only walk short distances, and be the cause of severe cramps. Other examples are patients with no feeling in their toes and or feet and severe discoloration of either the hand or foot.
A general condition has been identified in this disease as being part of an autoimmune syndrome manifesting as a general inflammatory condition of the vascular system, more specifically vasculitis. Vasculitis may be considered an inflammatory syndrome with structural alterations of the vascular wall, complicated by lumen occlusion, leading to tissue ischemia. Vessels of any size may be altered in systemic vasculitis but in cutaneous forms alteration affects small vessels, especially those post-capillary. The various forms differ by age of onset, affected organ, and presence of periods of remission and exacerbation, amongst other features. Sometimes they may also be superimposed to other well-defined diseases, as vascular disorders, identified as secondary conditions such as neoplasia, allergic reactions, and infections.
Infections can promote inflammation of the vascular intima wall of any diameter and in any organ. Palpable purpura is the most common manifestation of vasculitis, although erythematous macules, nodule, ecchimoses, erosions, ulcerations, hemorrhagic blisters, necrosis, and gangrene may also occur. Skin can be the target organ in this type of vascular pathology. The relative frequency of vasculitis of the skin may be the first manifestation of a very severe systemic disease.
Relative and or absolute ischemia caused by vascular disease such as sclerosis resulting from aging, results in compromised poor blood flow to tissues and cells. This results in a lack of nutrients and oxygen at cellular level from reaching the cells, with the resulting symptoms of ageing. This is manifested by such symptoms as a loss of mental agility, alertness, memory loss and other conditions commonly seen in senescence. In normal metabolism most of the metabolic energy is used to maintain gradients across the cell membrane. The provision of nutrient substrates is recognized as the best basis for maintaining a level of metabolic activity and ongoing energy needs in the cell. In these instances diseases as manifested by neurodegeneration of aging may also be modulated. Because neuron function can be disrupted by many substances in the blood, it is necessary to target the central nervous system by means of carrier fluids capable of breaching the blood brain barrier by introducing charged and or lipid substances into the blood may accomplish this. It is known that chemical communication in the brain may be influenced by nor epinephrine, acetylcholine, seretonin, endorphin and many other naturally occurring chemicals in the brain.
The effects of aging may be attributed, on a molecular level, to the oxidative processes in the cell which is harmful to proteins, lipids and nucleic acids. By providing sufficient anti-oxidants, it may be possible to modulate or even reverse the effects of aging at molecular level. Biological aging processes are part of the increase in disorder at cellular level with the acknowledged difference being that in the case of a pathological multi-system, atrophy or senescence at cellular level, multi-organ failure may occur. This process is demonstrated by reduction in cellular mass of the organs and may be seen in the aged on autopsy. For instance, the human brain can decrease from an average weight of 1500 grams to less than 1000 grams in advanced age.
The senescent organ loses many functions, leading to premature aging, for instance the brain loses its memory retention capability, cannot react quickly to external stimuli and is unable to memorize new information. Loss of mass is also demonstrated in organs such as the liver, kidneys, lymph nodes, skeletal muscle and bones. Corresponding changes are seen in depleted fat deposits, skin elasticity, brittle bones, low resistance to infection, lack of exercise tolerance and reproductive ability. At the cellular level, aging means inadequate DNA repair, leading to disorder in cell replication Loss of mitosis in the nucleus of the cell, followed by a closing of the microcirculation. This results in so-called cell drop-out and loss of organs, as well as membrane function, in particular the TNP or transmembrane potential. This process is progressive and affects all organs and tissues throughout the body. The etiology and pathogenesis of this condition involves a universal and fundamental aspect of cell physiology.
In any study on aging, two distinct types of cells must be considered. These include normally dividing cells and post-mitotic cells, normally dividing cells are those of the skin, hair and gastrointestinal tract. Thousands of such cells die daily, but are continually replaced with exact replicas until the time of aging begins. This begins in the mid-twenties in humans. The second cell type is that which makes up the central nervous system, brain and heart. In general, post-mitotic cells do not divide or reproduce. Humans are born with a fixed number of post-mitotic cells, which lose function and die daily throughout the human life span. Death, as a result of aging, occurs when a critical number of post-mitotic cells lose function within a critical organ, such as the brain.
Congenital defects and infectious disease can strike anywhere. One of the most common diseases occurs in the arteries: atherosclerosis. Blockages can occur in veins as well as in arteries, but these tend to be caused by blood clots, or thrombi, rather than by atherosclerosis. Thrombophlebitis (or often called phlebitis) most commonly involves clotting of blood and inflammation of a vein in the leg. This can be serious if a portion of the clot becomes detached, travels through the heart and gets pumped to the lung where it blocks a pulmonary artery as a pulmonary embolism. About 10% of people with pulmonary embolism die within an hour. Clotting of blood in the veins can occur when blood flow is slow or stagnant. This can occur during long periods of immobilization such as when a person is confined to a hospital bed, cramped in a crowded airplane on a long flight or driving for an extended period.
Atherosclerosis (hardening of the arteries) occurs “naturally” with aging as a result of cross-linking of macromolecules like proteins and polysaccharides. Atherosclerosis refers to the formation and hardening of fatty plaques (atheromas) of the inner surface of the arteries. In atherosclerosis, the arteries not only harden, they narrow, sometimes narrowing so much that hardly any blood can get through. Such narrows vessels are easily blocked by constriction or objects in the bloodstream.
The internal surface of an artery is covered with a single layer of endothelial cells that are pressed against each other like flagstones on a terrace. Atherosclerosis begins with injury to endothelial cells, exposing portions of the artery surface below the endothelium. Free radicals, chemicals in cigarette smoke or other irritants could be responsible for the injury, as could turbulence and mechanical force due to high blood pressure. Platelets (round cells half as large as red blood cells) clump around the injured endothelial cells and release prostaglandins, which cause the endothelial cells to proliferate like cancer. LDL-cholesterol particles release their fat into the areas made porous by prostaglandins. Macrophages (scavenger white blood cells) engorge themselves on oxidized LDL-cholesterol until they become unrecognizable “foam cells” that invade atheromas. Then the atheromas are hardened by fibrin (which forms scar tissue) and finally by calcium patches. A vicious circle often arises with scar tissue attracting more platelets and LDL-engorged macrophages. Atherosclerosis can occur in any artery. Most commonly it occurs in the aorta, the artery that receives blood directly from the heart. Since the aorta is the largest artery in the body, it is rarely critically narrowed by atheromas. Nonetheless, atherosclerosis can contribute to aneurysms (ballooning of an artery, responsible for only one-fortieth of the mortality rate of heart attack—an aortic aneurysm killed Albert Einstein, who refused to be operated upon.) The most frequent life-threatening problems, however, are caused by the arteries supplying the heart, the brain and the kidneys, in that order.
Since the blood is 80% water, fats will not dissolve in the blood. Therefore, fats need to be attached to carrier molecules to travel through the bloodstream. The principle carrier molecules for fat are albumin, chylomicrons, Very Low Density Lipoprotein (VLDL), Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). Free Fatty Acids (FFAs) are attached to albumin, whereas triglycerides are mainly transported by chylomicrons and VLDL. Cholesterol and phospholipid are primarily transported by LDL and HDL. Cholesterol is supplied to cells primarily by the attachment of LDL to specific LDL receptors on cell membranes. Thyroid hormone lowers blood cholesterol by increasing the number of LDL receptors on cells. For most people, atherosclerosis due to excessive LDL-cholesterol in the blood is the result of a high level of dietary saturated fat resulting in high LDL-cholesterol production by the liver. The primary function of HDL seems to be to remove excess cholesterol from the bloodstream. LDL can directly release cholesterol into arterial areas made porous by prostaglandins—whereas HDL can scoop up this loose cholesterol and return it to the liver. Thus, HDL deficiency can be as serious an atherosclerosis risk as LDL-cholesterol excess. A 1% reduction in blood cholesterol is generally associated with a 2% reduction in risk of coronary artery disease, within “normal” levels of blood cholesterol.
Free fatty acids are a major source of energy for many organs, including the heart. Triglycerides are hydrolyzed into FFAs and glycerol by the enzyme lipase, which is found both inside cells and on the surface of the endothelial cells of capillaries. Phospholipid is an essential constituent of cell membranes. Cholesterol is also an essential constituent of cell membranes, particularly in the nervous system. Cholesterol is also the principle precursor of cortisone and sex hormones. 93% of cholesterol is found in cells and only 7% in plasma.
The coronary calcium scan is a test that assists in showing whether a patient is at risk of developing a coronary artery disease (CAD), by determining the presence of plaque (fatty deposits) in blood vessels. The presence and amount of calcium detected in a coronary artery indicates the presence and amount of atherosclerotic plaque. Since calcium deposits appear years before the development of heart disease symptoms such as chest pain and shortness of breath, a coronary calcium scan is most useful for people who are at moderate risk of having a heart attack within the next 10 years, and may help doctors decide whether a patient needs treatment. The calcified plaque burden caused by calcium deposits is measured with the Calcium Score, also called the Agatston Calcium Score, which is computed for each of the coronary arteries based upon the volume and density of the calcium deposits. The calcified plaque burden does not correspond directly to the percentage of narrowing in the artery but does correlate with the severity of the underlying coronary atherosclerosis. The score is then used to determine the calcium percentile, which compares the calcified plaque burden in a subject to the calcified plaque burden in other asymptomatic men and women of the same age. The calcium score, in combination with the percentile, enables the physician to determine the risk of developing symptomatic coronary artery disease and to measure the progression of disease and the effectiveness of treatment.
A score of zero indicates the absence of calcified plaque burden and significant coronary artery narrowing, although it does not entirely rule out the presence of soft, non-calcified plaque or the possibility of a cardiac event. A subject with a score of zero has a very low likelihood of a cardiac event over at least the next 3 years. A score greater than zero indicates at least some coronary artery disease. As the score increases, so does the likelihood of a significant coronary narrowing and coronary event over the next 3 years, compared to people with lower scores. Similarly, the likelihood of a coronary event increases with increasing calcium percentiles.
Often, there are no symptoms of underlying cardiovascular diseases and a heart attack or stroke may be the first warning. Early medical detection and treatment is available, however, is not always effective. Angiograms, bypass surgery and angioplasty are invasive and traumatic procedures associated with high cost and often requiring additional therapy and/or intervention.
The use of chelating agents of various types to entrap metal ions useful in magnetic resonance imaging is well known. Generally, the chelating agents contain a substantial number of unshared electron pairs or negatively charged or potentially negatively charged species. Perhaps the simplest among these is ethylenediaminetetraacetic acid (EDTA) commonly used as a water softener. However, many such agents are known, including, most notably, and commonly used, diethylene triamine pentaacetic acid (DTPA) and tetraazacyclododecanetetraacetic acid (DOTA) and their derivatives. U.S. Pat. Nos. 5,573,752 and 6,056,939, disclose derivatives of DOTA which are coupled to a benzyl or phenyl moiety wherein the phenyl ring is substituted by isothiocyanate. This isothiocyanate provides a reactive group for coupling to various additional compounds. As described in these patents, the isothiocyanate group can be used to couple the chelate to a targeting agent such as an antibody or fragment thereof.
However, many conditions and diseases are brought on by damage at the cellular and intracellular level. Often the mechanisms for cellular repair are inadequate or so compromised the cells cannot recover or the mechanisms that cause the damage simply overwhelm the cell. The clinical significance of the damage generated in living cells is manifested in a diseased cell or symptoms of an underlying condition. It would be beneficial to develop methods to facilitate the inhibition of cellular damage or boost recovery. The presently disclosed subject matter addresses, in whole or in part, these and other needs in the art.